Episode 85: Essential Cardiovascular Risk Laboratory Analysis with Dr. Thomas Dayspring

What a superb conversation with leading expert lipidologist and – importantly – clinician of 30+ years, Tom Dayspring, MD. In this tour-de-force conversation, we break down the essential cardiovascular risk laboratory analysis you need to be undertaking on all your patients. We spend a little extra time on Lp(a) and the coronary calcium score. Our conversation is incredibly practical; I was fervently taking notes through the entire recording, as I suspect you’ll be doing! I will likely bring Tom back for additional conversation, perhaps focusing on women’s health, so stay tuned!

As with many of my podcasts, I chat with my guests before and after the recording. Tom and I discuss on the podcast whether we’re concerned about brain cholesterol deficits with an excessively lowered LDL. He unequivocally stated not; we synthesize all the cholesterol we need locally, including in the CNS. However, after the recording, he added that statins can cross the BBB and lower brain cholesterol. Serum desmosterol is an analyte that can readily be assessed that is a surrogate marker of brain cholesterol: consider this if needed.

Enjoy this in-depth conversation, and be sure to leave New Frontiers a rating on iTunes or Stitcher or wherever you listen. It’s the best thing you can do to help share this valuable content and help put FxMed in front of more and more listeners! Thank you! ~DrKF

A Functional Medicine Perspective on Lipidology with Dr. Thomas Dayspring

A few months ago, Dr. Fitzgerald explored the world of lipidology and, specifically, lipoprotein (a) in a blog post. The post generated so many questions that we decided to do a deeper dive into the subject in this episode of New Frontiers. Dr. Thomas Dayspring is a leading voice in the field of lipidology. He’s an internal medicine doctor and a Fellow of the American College of Physicians and the National Lipid Association. He’s lectured all over the world on clinical lipidology and he’s published book chapters and peer reviewed journal articles. He also serves as the associate editor of the Journal of Clinical Lipidology. In this episode, Dr. Dayspring talks with Dr. Fitzgerald about primary, secondary and tertiary laboratory analysis for cardio assessment.

In this episode of New Frontiers in Functional Medicine, you’ll learn about:

Thomas Dayspring, who resides in Richmond, VA is a Fellow of both the American College of Physicians and the National Lipid Association and is certified in internal medicine, and clinical lipidology. Prior to locating in VA in 2012 and serving as Chief Academic Advisor for two major CV laboratories, he practiced in NJ for 37 years. Career wise he has given over4000 domestic (all 50 states) and international lectures, including over 600CME programs on atherothrombosis, lipids/lipoproteins (and their treatment), vascular biology, biomarker testing, and women’s cardiovascular issues. He has authored several manuscripts and lipid book chapters. He isan Associate Editor of the Journal of Clinical Lipidology. He was the recipient of the 2011 National lipid Association’s Presidents Award for services to clinical lipidology.

• Twitter @Drlipid

Dayspring Work-Up Algorithms

Dayspring: Clinical Biomarkers slides

Triglycerides and cardiovascular risk: Apolipoprotein B holds the key

JAMA Cardiology: Apolipoprotein B Particles and Cardiovascular Disease: A Narrative Review

Lipoprotein(a) mass: A massively misunderstood metric

Identification of a new plasma biomarker of Alzheimer’s disease using metabolomics technology

2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk

NEJM: Lipid Management for the Prevention of Atherosclerotic Cardiovascular Disease

Alzheimer’s Disease: Brain Desmosterol Levels

Dr. Kara Fitzgerald: Hi everybody, welcome to New Frontiers in Functional Medicine where we are interviewing the best minds in functional medicine, and today of course is no exception. A couple of months ago, we wrote a blog on LPA. If any of you saw that blog, you’ll see that we were just touching on it and yet it was a pretty extraordinary drill down. And I just realized many more questions exist in the world of lipidology and it was high time that I brought an expert onto the podcast to move through what we want to look at as clinicians and how we want to think about it and what kind of interventions we can do, etc.

That brings me to my guest today. I’m just really excited to be speaking with him and I’m just so glad that our paths crossed. He’ll probably be joining me more than one time. And actually, send me your questions since this is likely the case. I’m speaking with Dr. Thomas Dayspring today. He is a Fellow of the American College of Physicians and the National Lipid Association. He’s an internal medicine doc. He has been practicing medicine for over 35 years, so he is an in-the-trenches clinician, but he’s also a clinical lipidologist. He’s been chief academic advisor for two cardiovascular labs. He’s lectured all over the world on clinical lipidology. He’s got book chapters. He’s got peer reviewed journal articles. He’s the associate editor of the Journal of Clinical Lipidology. He’s just a really smart guy. He was the recipient of the 2011 National Lipid Association president’s award for services to clinical lipidology. He knows what he’s talking about in the science, and really most importantly for all of us, he has been in the clinical trenches. He’s been applying all of the scientific knowledge and addressing these things with patients for decades. Tom, welcome to New Frontiers.

Dr. Thomas Dayspring: Well, it’s a pleasure to be here speaking, Kara. I know you have an enlightened audience that it should be very fun, the topics we’re about to get into.

Dr. Kara Fitzgerald: Yeah. Originally, LPA brought me to you, but as you and I have been dialoguing, we just really kind of a-ha’d on the best use of our time, at least for this first conversation, is you as a scientist, as a lipidologist and a clinician to move through the lab panels that you’re thinking about and why. We’re going to break it up today into a primary, secondary and tertiary laboratory analysis. And let’s just jump right in with what kind of a primary cardio evaluation is essential in your opinion?

Dr. Thomas Dayspring: All right. Well, as everybody knows, cardiovascular morbidity, mortality is high on the list to evaluate in a human being and make sure if issues are discovered, you’re going to do whatever you have to do using lifestyle, and for the very high-risk people, pharmacotherapy. What is the workup? And of course, me being who I am, we’re going to concentrate on the lipid lipoprotein workup, although cardiovascular risks require a complete personal history of family history, a good physical examination, lifestyle evaluation, etc., etc. Well, you’re going to have to order some biomarkers to further ascertain and better qualify what degree of cardiovascular risk might somebody have. And depending on what you at the end of the day come to, you’re going to base the aggressiveness on your treatment on geez, what risk category are you in? Low risk, moderate risk, high, very high risk.

Of course, everybody’s going to start with some standard blood tests, a CBC, and you’ll deal with whatever shows there. You going to do a urinalysis, and to me the most important thing in the lipid world to look out for that is is there any protein in the urine. That’s a marker of endothelial dysfunction.

Dr. Kara Fitzgerald: You’re going to just do a basic UA. Are you going to look at microalbumin or anything like that on this initial one?

Dr. Thomas Dayspring: Yes. Most basic dipstick is going to have a microalbumin on it. I don’t think you have to quantify it beyond that. I mean, there’ll be other things in there that would be of value, and so as a lipid guy that’s  primarily what I’m zeroing in on, it’s the protein in the urine, because that tells me you have glomerular endothelial dysfunction, and if you have it there, you have it elsewhere, and it’s a big risk factor. It’s a prediabetes risk factor, metabolic syndrome risk factor, blah, blah, blah. All right. And of course, everybody’s going to do a complete metabolic profile. So you’re going to get a glucose, you’re going to get at least a creatinine, and more important in looking at the creatinine, virtually, all labs report estimated glomerular filtration rate, EGFR, and that’s the critical metric. It will be adjusted if you’re an African American as compared to a Caucasian.

And here is a big problem with that, because again, if you start slipping with EGFR, it’s a major cardiovascular risk factor, and all labs sort of report it’s under 60 or it’s above 60. Try and get your labs to give you an exact EGFR because many don’t recognize this, if your EGFR is between 60 and 90, which many labs will say, hey, that’s normal, that’s stage one kidney disease according to the kidney societies. And to me, that’s aha, I’ve got a kidney issue here. That’s the grand opportune time to recognize I need a more serious renal workup in this patient. I don’t want to wait till you’ve lost a third or a half of your kidney function and your EGFR is 60 or below. So take mention to that EGFR number. It’s a major kick in the rear end that you better look seriously at this patient for-

Dr. Kara Fitzgerald: And we need to be working with a lab that’s going to quantify regardless.

Dr. Thomas Dayspring: Yes. Right now, too many just say above 60, below 60, and above 60 they consider okay. I could settle on 90 for that if they wanted to do, but I think you’ve got to know if it’s between 60 and 90, because before you get to 60, you’re going to be 70, and I would know that before you lose too much of your kidney function.

Dr. Kara Fitzgerald: Absolutely. Absolutely. Listen, 30 seconds, what is the secondary workup for kidney disease you’re going to be doing?

Dr. Thomas Dayspring: Well then, personally I would rather see a cystatin level. It’s a much better blood biomarker of renal function because it’s not influenced by body mass and race the way creatanine is, but that’s the second. And if that is also high, then I think you would get an ultrasound of the kidney and to see what you’re dealing with. If you haven’t checked urinary protein or other abnormalities in the urinalysis, you would do that, and that’s where you start. Between those, I think you’d have a good handle that I’ve got a problem here. Any single biomarker that’s abnormal, it’s never bad to, Oh, let me repeat it in two or three weeks to make sure it’s not a fluke before you do the million-dollar workup. I think that’s the approach to that. And start going down and then you can get a handle.

Of course, you’re going to look closely at blood pressure in anybody who might have impair … You’re going to look closely for insulin resistance biomarkers. You’re going to question a family history, just hope, my God, that everybody in his family’s got polycystic kidney disease, something crazy like that. So yeah, you look at it.

Dr. Kara Fitzgerald: Let’s keep going on our primary cardio workup.

Dr. Thomas Dayspring: All right. The last thing, I think you’ve got to really zero in on in the comprehensive metabolic profile, not that everything in there might not have importance, but I think it’s crucial to get an upfront idea is there any evidence of hepatic inflammation going on? And you know what I’m looking at, NASH or fatty liver. Of course, there’s a million causes of AST and ALTs going up, but the most troubling cause is insulin resistant early fatty liver. And if you’re AST and ALT, especially the ALT is elevated, I have to look further to decide, my God, you have fatty liver, because not only is fatty liver now the leading cause of cirrhosis end stage liver disease and liver transplantation, it’s so tied in with diabetes, prediabetes, insulin resistance, and there are ways we can address that nutritionally and even pharmacologically if we have to to preserve your liver. Livers do not last forever. Too many doctors see an ALT of 40, 50, just a little bit of elevation. Don’t worry about it. My God, that’s a potential down the road death sentence. So please workup abnormal aminotransferase.

Dr. Kara Fitzgerald: What’s going to raise your eyebrows? What’s the lowest?

Dr. Thomas Dayspring: Every lab might have a different reference range, so you certainly want it to be under whatever the upper limits of normal that are reference range. X person just think your ALT should be under 20, and if it starts to increase above 20, there’s something irritating your liver. Now, of course I mentioned insulin resistance. I think in today’s world, you have to immediately rule out the viral causes of chronic liver disease also. So Hey, it’s a, hepatitis B and C tests, etc. Hepatitis A perhaps. Once you’ve ruled them out, unless you’ve got some obscure liver disease, you’re looking at fatty liver, which is going to come down to you’re drinking too much or you’re insulin resistant and you’re not on the proper diet. And you can address that easily.

Dr. Kara Fitzgerald: You said to me earlier, I just want to quote you because I thought this was, I think it’s important, you said, everyone with insulin resistance has some degree of fatty liver, period.

Dr. Thomas Dayspring: It’s a very early manifestation of it. Tragically, it goes unrecognized until near end stage liver disease because too many clinicians poo poo it… Patients say, I see this ALT is up. What’s that? Don’t worry about it. It’s only up a little bit. There’s no such thing as a little bit.

Dr. Kara Fitzgerald: Let me just say to folks listening, I podcasted last year with Bob Rountree, and our whole conversation was on NASH, and he outlined just a great treatment protocol. He just went through all of the supplements and so forth. So I would just encourage you to check out Bob’s podcast or check out his transcript if you want those details. Because we’ve got Dr. Dayspring. We’ve got a lot of other topics here to cover.

Dr. Thomas Dayspring: We sure do.

Dr. Kara Fitzgerald: Keep going on that primary investigation.

Dr. Thomas Dayspring: Okay. So we’ve done that. Kara, you know, and some people will say if you’re going to see a lipid abnormality, you need a pretty thorough thyroid workup. Personally, I think every adult at least on your initial meeting needs some evaluation of their thyroid function, because we need to be euthyroid to prevent a lot of cardio metabolic disease, and if you don’t recognize that and don’t take care of that, you’re going to have a tough time controlling certain lipid and lipoprotein abnormality. I think if nothing else to TSH to reflex the Free T4, whatever thyroid workup a clinician might desire, I think that’s pretty crucial right up front also. That’s the basic stuff.

Dr. Thomas Dayspring: Now, I’m going to get into the lipid profile and some lipoprotein markers. Since you started off this conversation with lipoprotein, little a-LP with a small case-a next to it, that is the most common inherited genetic lipid lipoprotein abnormality that is significantly associated with cardiovascular risks. Now, you don’t get that because you’re eating wrong. You get that because you picked the wrong mother and father, but I don’t think you had much choice there. So that’s passed on to you. And if that concentration happens to be high, you automatically jump to a higher cardiovascular risk complication, which has treatment considerations involved with. To me, and at least last year, the European guidelines jumped on this. We believe everybody needs a onetime Lp(a) test somewhere in your life. Look, you don’t need it when you’re three-years-old, but as you hit 20, early adulthood, that’s your crucial lipid parameter. It’s a one-time test because it’s genetic. You either have too much of it or you don’t. It’s not going to change 30 years down the road. We need to evaluate that.

By the way, not only is it the most common monogenic cause of atherosclerosis, it’s also a mega cause of aortic valvular stenosis. And that’s certainly something you want to know earlier rather than later too. It’s a very crucial test. Apparently, you’ve done the podcasts on it already. It’s very complex world once you get into it, and I’d love to challenge everyone to look at it

Dr. Kara Fitzgerald: Well, you know what, we blogged on it, and I’ll link to that blog on our show notes so people who want to grab it, they can I. We’re going to talk about that Lp(a) workup because you’ve thrown out incredibly important points. And I want to ask you stuff like, well, there’s a continuum. Some people might have modest elevations and some people have severe elevations. I want to talk about all of it. We’re going to circle back to Lp(a). But I want to finish this primary evaluation first.

Dr. Thomas Dayspring: Okay. Good. Everybody’s going to get what’s called the standard lipid panel or lipid profile. And basically, that consists of a total cholesterol measurement. By the way, that refers to all of the cholesterol molecules that are in all of your circulating lipoproteins, all of them, regardless of class of lipoprotein. And look that’s used in some risk equation, so it’s an important marker. And if it was a chart, right away you got to be thinking of some familial cause of hypercholesterolemia. It’s a poor man surrogate of something. We’re going to talk about apolipoprotein B. But by itself, other than a population screening tool, it’s not that useful.

Dr. Kara Fitzgerald: Not useful.

Dr. Thomas Dayspring: Then they’re going to break it down into the component lipoproteins, how much cholesterol or triglycerides are they carrying? You see LDL cholesterol. What that refers to is that’s the cholesterol content of every LDL that’s circulating within a deciliter of your blood. And in most labs, it’s a calculated value based on other parameters. There are labs that will do a direct measurement of your LDL cholesterol, and I would suggest that’s probably a better way to get that value. Most labs use something called the Friedewald formula developed in the 1970s, which has probably outlived its usefulness. The John Hopkins people recently came up with a better formula, but why calculate it when you can measure directly LDL cholesterol? And the only value LDL cholesterol provides to you, it’s another poor man’s surrogate, better than total cholesterol, but it’s just a preliminary indication to you that this person may have too many atherogenic lipoproteins circulating in their blood. And we’re going to talk about it in a minute, but that’s your ApoB containing particles. So LDLC is a poor man’s guesstimate of ApoB concentration.

Of course, you’re going to see HDL cholesterol on the panel. That would be the cholesterol molecules carried in all of your HDL particles per deciliter of plasma. Certainly, tons of epidemiologic trials have shown people with low HDL cholesterol in general have higher cardiovascular risks than those who don’t have low levels of HDL cholesterol. All you can do is use that as a maybe. If you showed up in my office and you have a low HDL cholesterol, I got to start worrying that you probably have cardio-metabolic risk, but I’m going to need other tests to prove it. There are plenty of people with low HDL cholesterol who never get cardiovascular disease, and there are plenty of people with high HDL cholesterol who do not.

And HDL cholesterol metrics have taken a major hit in the lipid world over the last 10 years because of mendelian randomization trials and numerous clinical trials where modulating HDL cholesterol had no cardiovascular benefits. It’s fine as a risk assessment tool. That’s the last time you look at it. Whatever therapy you throw at a patient, I personally could care less what it’s doing to HDL cholesterol. You’re going to look at am I getting rid of atherogenic lipoproteins or not? And if you want a generalization, low HDL cholesterol is a just again, a surrogate that you probably have too many of these potentially atherogenic ApoB containing lipoproteins in your plasma.

Dr. Kara Fitzgerald: All right. We’re going to … Yup. Go ahead, finish that.

Dr. Thomas Dayspring: Everybody you see with low HDL cholesterol is likely early insulin resistance, prediabetes, diabetes, and their major lipoprotein abnormality is too many ApoB particles. So the low HDL cholesterol is a clue to you of that. That’s the other cholesterol measurement. Now of course, serum triglycerides, modern-

Dr. Kara Fitzgerald: Listen, wait, before you jump onto triglycerides, let me just ask you about HDL. There’s a lot of buzz in our world around “too high HDL”. Is that something that you’re going to think about? I mean, I’ll just use myself as an example. Mine, well, and my mom’s interestingly, just us, I’ve seen my whole family, the other side of the family actually has high LPA, which was the intro on that blog I was actually writing about my dad, but I don’t. I have an HDL that can run in the 120s. Am I worried about that?

Dr. Thomas Dayspring: Probably not. But you might have to be. And here’s the problem. HDL particles are very small. They don’t carry that much cholesterol. As you know, a middle of the road reference range would be for a woman, 50 to 60, for a man, 40 to 50. As you go higher and higher, that means you have to have big HDLs, otherwise, they couldn’t carry that much cholesterol. Well, everything comes down to HDLs now with, are they what we call functional HDLs? They have the capacity, the ability to do good things to your cardiovascular things or might you have dysfunctional HDLs which cannot do cardioprotective properties to your blood vessels. And so until we get a blood measure of HDL functionality of which there are zero available to us in the real world nowadays, we have plenty of studies that show as HDL cholesterol starts to go above 70, 80, certainly in your range above 100, it’s possible those are dysfunctional HDLs. They don’t carry the type of proteins they should be carrying and have cardioprotective abilities. They might not carry the other surface lipids that come into play, so I don’t know.

There are enzymes that are involved with HDL metabolism, one called cholesterylester transfer protein, where if you have some sort of change of function of that, your HDLs tend to be big. Some of those people are not a cardiovascular risk, some are. So it’s a conundrum. If you came to me and said, Tom, should I worry? Do I have dysfunctional HDL? I’d have to say, Kara, I got to look at every other biomarker I’m going to do on you. And because you have that, I’m probably going to do some extra ones and then I can, based on that, say you’re a cardiovascular risk or you’re not.

Dr. Kara Fitzgerald: What are the extra ones? Give me the quick run-down.

Dr. Thomas Dayspring: Well, that would be, we’re going to delve back into the markers of what I call potentially atherogenic ApoB containing lipoproteins. You got to look at inflammatory markers, insulin resistance type of markers, all of which affect HDL catabolism, metabolism, lipidation, liquidation. It’s a very complex topic.

Dr. Kara Fitzgerald: Is the map, is actually ensuring I’ve got some large alpha ones, is that a good piece of information for me?

Dr. Thomas Dayspring: No. First, it’s the big HDLs that tend to be dysfunctional, but, the majority of big HDLs are not dysfunctional. Without getting too complicated, what is an HDL supposed to do once it fills up with cholesterol? You’ve been taught that it’s supposed to bring it back to the liver in a process called reverse cholesterol transport. Well, if you really had very good reverse cholesterol transport, that would tell me if you’ve got all big HDLs, they’re somehow not being delipidated. There’s something broken in your HDL catabolism, because those HDLs should be carrying that cholesterol to wherever an HDL carries it, and it’s way more than the liver. Those HDLs can bring cholesterol to your steroidogenic tissues, they can bring it to your gut or can just transfer it to an LDL, which then is supposed to bring it back to the liver. So it’s very tough to just say you’ve got big HDLs to … I would never pat you on the back and say, don’t worry about it, you’re cardioprotective. That would be a dumb statement to make-

Dr. Kara Fitzgerald: Got it.

Dr. Thomas Dayspring: … without further … And too many, and it drives me nuts because I think I told you for much of my practicing career, my clinic in Northern New Jersey is called the North Jersey Institute of Menopausal Lipidology, so I was very much into women’s health, and nothing more annoyed me than clinicians who tell women they’re protected because they have high HDL cholesterol. They might be, but they might not be, and that is a dumb statement that no clinician should ever make henceforth. They need more education.

Dr. Kara Fitzgerald: Awesome. Well, you know what, you have made your point. I really appreciate it. For this podcast, my team will pull out really good quotes. Tom, you’re giving us a ton of them. We’ll blast that. We’ll blast that out without there. We’ll support your message. Okay. So then for me, again, this high HDL, but for anybody, you’re circling back to ApoB and triglycerides. Let’s talk about the additional biomarker journey you’re going to go on.

Dr. Thomas Dayspring: Well, I was about to stumble into triglycerides, which everybody knows. Triglycerides is a glycerol molecule carrying three fatty acids. They could all be the same fatty acids, they could all be different, you could have two of one, one of another, so it’s pretty complicated. But it’s a measure of fatty acids which don’t circulate for the most part in your bloodstream. Attached, they become glycerol lipids. They esterify to your phospholipid or they esterify to a glycerol molecule. So yeah, phospholipids and triglycerides carrying your fatty acids. Phospholipids are on the surface of all your lipoproteins. Triglycerides wind up in the core of your lipoproteins. When you get a serum triglyceride level, you are measuring the mass of triglyceride molecules that exist in every lipoprotein in your body. It’s LDL triglycerides plus HDL triglycerides plus intermediate density triglycerides plus Lp(a) triglycerides, VLDL triglycerides, and if it’s postprandial, could be chylomicron triglycerides. So that’s what it is.

And the way you use that, once it crosses a certain threshold, you have to automatically be thinking that I’m dealing with early insulin resistance, prediabetes, maybe it’s even a diabetic. Further blood tests would show that. But that’s where this marker becomes important.

Dr. Kara Fitzgerald: Where’s the threshold?

Dr. Thomas Dayspring: The real defining thing is what is the threshold? Virtually, all of our guidelines and laboratory reference range say, hey, if it’s above 150, it’s abnormal. I’m going to tell you, I personally worry when I see a triglyceride being much above 80 or 90 milligrams per deciliter in a human. Now, that doesn’t mean everybody with a triglyceride of 100 is a prediabetic. I would have to do other tests to see whether that’s true or not. Well, we’re going to have to start worrying about triglycerides at a much lower level.

And believe it or not, what is the importance of triglycerides? Well, they do change the properties of any lipoprotein if there’s too many triglyceride molecules within any lipoprotein, but they’re basically another poor man surrogate that this person has a high ApoB level. And so boom, you’re going to … I keep mentioning ApoB here. That’s going to be the wonder marker that everybody has to do. But before you measure ApoB, the guesstimates from a lipid profile is, Hey, if there’s elevations of total cholesterol, LDL cholesterol or non HDL cholesterol or triglycerides, I’m probably dealing with a high ApoB situation here. Say I probably am dealing with it, we’re going to measure ApoB and then you know I’m dealing with it or I’m not. And that should be at the head of the list.

Dr. Kara Fitzgerald: And I just want to remind you guys ApoB is part of Dr. Dayspring’s primary workup. Listen, what’s an optimal triglyceride level before we jump into ApoB?

Dr. Thomas Dayspring: Well, I just told you-

Dr. Kara Fitzgerald: Less than 80.

Dr. Thomas Dayspring: … your physiologic triglyceride is well under 70, probably 40 or 50. If you have perfect metabolism, perfect nutrition, that’s what it probably should be. Current guidelines are going to tell you if it’s above 150, some are speaking down to 130 now, that we’re worried about you. This is an abnormal chart. 130 would be the 75th percentile. That means 75% of people would have a lower triglyceride than you. So you’re crossing into the territory. I think there are some new publications about to come out that are going to show you we have to start worrying at much lower triglyceride levels. Look, people who know me know for most of my life I was sort of an obese guy, not paying much attention to stuff and had high ApoB levels. I never had a triglyceride above 102. And all my life until we knew this all, we were at a great triglyceride level. If you have it, if you’re insulin resistant like I was, a triglyceride of 100, you better seriously look at other markers, especially ApoB, so it varies, but respect triglycerides, please.

Dr. Kara Fitzgerald: Awesome. Yeah. 40 to 50, I got it. Yup. That’s the range that we’ve been using. Let me just-

Dr. Thomas Dayspring: One last little pearl on triglycerides, because yeah, I told you low HDL cholesterol is a pretty good marker of early insulin resistance, diabetes. Why is HDL cholesterol so low in diabetics? Because what do they all have? Escalations of triglycerides. And HDL particles should virtually carry very few if any triglyceride molecules. But if you have too many triglyceride molecules, they crash their weight into HDL particles knocking cholesterol molecules out. So if you have an HDL carrying excess triglycerides, of course you’re going to have a low HDL cholesterol. They’re called fat HDLs. Bad news.

Dr. Kara Fitzgerald: Interesting. Okay. So then in that case, an HDL triglyceride ratio would actually be useful.

Dr. Thomas Dayspring: Yeah. Many people think they go hand in hand, but I would tell you it’s the triglycerides that drive that ratio, and it’s the triglycerides that drive the low cholesterol content of your HDL. So if you want to use that ratio as a surrogate of insulin resistance, go ahead. I think if you just looked at lower triglyceride levels, you wouldn’t even need that ratio. But yes, there’s certainly a mega interplay, because lipoproteins, every one of them, exchange cholesterol for triglycerides. So particles that have too many triglycerides send it over to particles that don’t, and to make room for that acquisition of the triglycerides, they send their cholesterol back to the particles they’re exchanging with. So HDLs become very triglyceride rich, they’re cholesterol poor. A triglyceride rich HDL is exposed to certain enzymes, so they all create small HDLs. One of the major factors behind the size of your HDL particle is basically triglycerides.

Dr. Kara Fitzgerald: Whether they’re there or not. Okay. Let’s keep on going.

Dr. Thomas Dayspring: The last thing can be, and I should mention because for people who for whatever reason aren’t going to do the ApoB test, the absolute best surrogate, meaning guesstimate in the lipid profile that you have too many of these atherogenic particles is something called non-HDL cholesterol. You take your total cholesterol level, which is a direct measurement, you subtract from it HDL cholesterol, which is a direct measurement, and what you’re left with is the cholesterol that is not in your HDL particles. Well, every other particle it’s left behind once you get rid of the HDLs is an ApoB particle. So non HDL cholesterol is the best correlate in the lipid profile that, my God, we’re dealing with too many ApoB particles here. We have cardiovascular risk and we better address it. It’s a free calculation. More and more labs are reporting that now. If they’re not, it’s a calculation you should do yourself. Unless you’re going to measure ApoB, then I’m not so sure you need it in every person. But it’s pretty much standard reporting nowadays, non HDL, because it’s in all the guidelines as a secondary goal of therapy after LDL cholesterol.

Dr. Kara Fitzgerald: I’ll just pop that calculation on our show notes.

Dr. Thomas Dayspring: Yes. Total cholesterol minus HDL cholesterol. If your lab isn’t reporting it, please try it yourself, put it in your flow sheet.

Dr. Kara Fitzgerald: Okay. Okay. Perfect. Any optimal non-HDL?

Dr. Thomas Dayspring: Yeah. It’s basically you get into the argument of what’s optimal for an LDL cholesterol or another, the two better surrogates of ApoB. And to be honest with you, it depends. If I’m talking to a patient who’s had a bypass and three stents, I want their LDL cholesterol and non-HDL cholesterol to be way lower than I do for somebody who’s early in the game, young, has had no cardiovascular issues yet. So any goal of therapy depends on your overall cardiovascular risk. But physiologically where normal LDL cholesterol would be 30 to 40, a normal non-HDL cholesterol to me should be under 70. The guidelines might still tell you 100, but the guidelines got some catching up to do.

Dr. Kara Fitzgerald: Okay. Wait, for non-HDL, you’re saying it should be around … a non-HDL cholesterol should be around 70?

Dr. Thomas Dayspring: Should be 70 or below. Again, if you have couple of bypasses, stents, terrible cardiovascular risk, the lower the better. Any surrogate of ApoB in people who have cardiovascular risk, the lower the better.

Dr. Kara Fitzgerald: And an LDL, you said, an optimal LDL?

Dr. Thomas Dayspring: And remember, you should say LDL cholesterol.

Dr. Kara Fitzgerald: Yes, LDLC.

Dr. Thomas Dayspring: LDL is a lipoprotein, so we’re measuring the cholesterol. Most guidelines nowadays, certainly for anybody in a treatable at-risk category, they’re talking about 50 or below.

Dr. Kara Fitzgerald: Really?

Dr. Thomas Dayspring: No one’s come out with LDLCs of 20, for god sakes.

Dr. Kara Fitzgerald: Really?

Dr. Thomas Dayspring: That’s about physiology. Remember, LDL’s primary job is they’re not delivering cholesterol to your tissues. You can’t hurt any tissue by dropping LDL cholesterol. LDL’s primary purpose is to bring cholesterol back to the liver or the small intestine. They are a major part of your reverse cholesterol transport system. And most of the animal kingdom has LDL cholesterol in the 20 to 30 range. Humans for a variety of reasons have higher levels, probably our lifestyle, a little bit of our genes, but you cannot hurt anybody who’s at risk by lowering their LDL cholesterol-

Dr. Kara Fitzgerald: Well, let me ask you this …

Dr. Thomas Dayspring: LDLs not delivering cholesterol to your adrenal gland, your gonads or any … every cell in your body has enough machinery to make all the cholesterol it needs. They don’t need deliveries.

Dr. Kara Fitzgerald: All right. Well, this is a big statement and especially for functional medicine doctors, anybody treating dementia is going to be perking up and get their fighting gloves on.

Dr. Thomas Dayspring: Yes. But let’s get rid of that issue right now. The brain makes all its cholesterol. There’s no lipoprotein that delivers cholesterol to the central nervous system. So whatever we’re doing with plasma lipids has zero effect on your brain lipids. Cholesterol is synthesized de novo in your brain. And so your inner making, you don’t know if your brain is not making enough cholesterol, that’s an issue for dementia, but it has nothing to do with the amount of cholesterol in your LDL particles, because they can’t cross the blood brain barrier and deliver cholesterol.

Dr. Kara Fitzgerald: Okay. All right. Well, that’s just really interesting. I’d love to sort of move into a keyed-up conversation, but well-

Dr. Thomas Dayspring: Yeah. There are lipid markers you can do to assess brain cholesterol homeostasis, but that’s beyond today’s talk.

Dr. Kara Fitzgerald: Okay. People will be tuning in to our next one for sure with with these. Okay. Keep going. Have we made it to ApoB yet?

Dr. Thomas Dayspring: So yeah, those are your standard lipid tests. Basically, I think the only reason you need that lipid profile is to see what a triglyceride level is, because what you really need, the people who get atherosclerosis have sterols in their artery wall. And the only way sterols get into the artery wall … by the way, without sterols, the most frequent one of course is cholesterol, but there are others. The only way a sterol gets into your artery wall is if a lipoprotein delivers it to the artery wall, and the lipoproteins that have the potential to pass through your endothelium and deposit that cholesterol within the macrophages causing foam cells plaque are your ApoB containing lipoproteins. So if I knew you had plaque, maybe you’ve done a CIMT study, a coronary calcium score or you had a myocardial infarction, I know, wow, obviously cholesterol got into your artery walls, and I know the way they got there is they were passengers inside of an ApoB containing lipoprotein.

So what is the primary driving force that an ApoB particle leaves plasma instead of returning to the liver and enters your artery wall? And by far the primary driving force is the quantitation, the number of LDL particles or other ApoB containing lipoproteins that force them into the artery wall. That’s why. Every LDL particle, every VLDL particle is enwrapped with a single structural, what’s called an apoprotein, a surface protein called apolipoprotein B, ApoB for short. There’s one ApoB on every LDL, one ApoB on every VLDL. Because of its very long half-life compared to VLDLs, days versus hours, 95% of your ApoB molecules are on LDL particles. If I measure ApoB and it’s high, I know you have too many circulating LDL particles. And if you do the odds are good that some of those are going to crash your endothelial barrier and wind up in the artery wall where they can promote atherogenesis. That’s why it’s such an important risk factor.

And this is backed up by dozens and dozens of epidemiologic trials, clinical therapeutic trials, genetic studies, that it’s a causal risk factor, having too many atherogenic ApoB containing lipoproteins. But remember, high ApoB, almost all of those particles are LDLs. Not that VLDL particles aren’t bad. You don’t want to have too many of them, they’re called remnants, but LDLs are the primary driving force of atherosclerosis.

Dr. Kara Fitzgerald: And where do you want to see an ApoB at?

Dr. Thomas Dayspring: A physiologic ApoB would be under 60 milligrams per deciliter. The average person walking around probably is in the 90s. People, when you start going above 100, you’re into the 80th 90th percentile reference ranges of ApoB, and those are people that need some sort of serious therapeutic approach, including lifestyle, and if needed to get where you got to go based on their risk pharmacologic ApoB lowing therapy. Those are the reference ranges. Surely if you’re a very high risk persons, had coronary disease, European guidelines are calling for under 55 now for ApoB.

Dr. Kara Fitzgerald: How are you going to be lowering ApoB?

Dr. Thomas Dayspring: Well, what is the primary cause why people have too many of these LDL and VLDL particles? Because their liver is not clearing them. The liver has been hopefully graced with the ability to upregulate something called LDL and VLDL receptors, which grab these ApoB particles and pull them into the liver, which can catabolize them and do lots of things with them. But if the liver clears them, obviously they cannot crash your coronary arteries. So you have to improve clearance of ApoB containing lipoproteins. There are many lifestyle measures that can help you address this situation to improve expression of the LDL receptors, decreased production of triglycerides and things like that that contribute to having unclearable LDL particles.

There’s many ways to pick the proper diet. Two, three months later, see if that diet’s working. Did your LDL or ApoB level go down? If it did, you’ve stumbled onto the right diet. And I shouldn’t say stumbled on cause hopefully you’re prescribing dietary therapy based on the rest of your metabolic workup, which we haven’t talked about. Are you insulin resistant or not? Am I dealing with a genetic cholesterol problem here? All of that might affect which diet you want to recommend to a patient, so you have to….

Dr. Kara Fitzgerald: Overwhelmingly though, people are going to want to have … Some clinicians are going to want to have some kind of an idea of where you’re starting from. And I’m going to assume you’re looking at insulin resistance as the causal factor.

Dr. Thomas Dayspring: Yes. Off the top of my head, I’m going to say in real world practice where I spent most of my life, 37 years of it, 90% of your ApoB elevations, you’re going to find underlying insulin resistance, prediabetes, diabetes, metabolic syndrome, high triglycerides, low HDL, cholesterol. Those are the people where I think, even just based on that, I mean, everybody’s going to do a A1C, you’re going to do perhaps an insulin level to get a better handle on that. But that’s where you-

Dr. Kara Fitzgerald: Well, you argue that the insulin level is actually really pretty important.

Dr. Thomas Dayspring: Yeah. We didn’t get into that up top because I was dwelling on lipids, but everybody’s going to get a glucose on their metabolic profile. I think an A1C is a pretty standard test. Realizing it’s not the Bible, there are people with elevated A1C, who are not diabetics, but most of them would be have some degree of glycemic abnormalities that probably need to be addressed there.

Dr. Kara Fitzgerald: But the reverse is true too, Tom. I mean you can see … I’ve certainly seen in my practice, particularly in women with PCOS have a beautiful A1C in their fours. I’m thinking of one woman in particular, she’s got an insulin of 30.

Dr. Thomas Dayspring: Oh yeah, but it’s a very insulin resistant disease. Sure. That’s where an insulin level might help you and there are other markers of insulin resistance beyond today’s discussion that might be appropriate for that patient. But I think you could nail down pretty easy that a PCOS is insulin resistant based on even certain hormonal markers or a adiponectin and other things including an insulin level. And again, off the top of my head, if you’re dealing with PCOS, you better be thinking insulin resistance is at play here, because it almost it’s a big part of that picture.

Dr. Kara Fitzgerald: It always is. Yeah.

Dr. Thomas Dayspring: Low-carb diet is probably the initial thing you’re going to go to. And with low carbs, your audience is more expert than I am is some you’re going to transition to at least a partially ketogenic or maybe a fully ketogenic diet because you’re getting rid of carbs, at least the simple not so good carbs for you out of your diet and you’re replacing that with some type of fat or protein probably. You’re going to individualize your recommendations for fat. For a fully ketogenic diet, extremely low carbs, it could work very well in this person, but a couple of cautions there. One, not everybody is going to want to stay on that severe ketogenic diet for a long time. If you’re going to do that, you really have to be doing finger sticks, checking on your ketones to really see am I really in a ketogenic state or not, because it’s a tough threshold to cross.

But the big worry nowadays, and it’s another whole lecture here is upwards of 40% of people who go on fully ketogenic diets send their ApoB level to high levels or through the roof. And boy, that becomes a whole issue, do I have to worry about that or do you not? Every other study in the history of world says you have to worry about high ApoB. Whether ketogenic induced ApoB is going to be an exception to that rule, somebody would have to do a major clinical trial to prove that.

Dr. Kara Fitzgerald: What’s your opinion? What’s your opinion?

Dr. Thomas Dayspring: My opinion is if you have cardiovascular risk and I’m blowing your ApoB into the stratosphere with a ketogenic diet, I want to make sure I have every other cardiovascular risk factor under control. Two, that’s where a coronary calcium might help you. And the number three is: in the ketogenic diet, back off the saturated fat and start using more mono-unsaturated fat or the polyunsaturated fat. There are more and more I’m starting to see by colleagues who know what they’re doing on the internet, there are vegan ketogenic diets and that might be the way to go in somebody who’s too much saturated fat.

Dr. Kara Fitzgerald: How frequently can you evaluate ApoB to gauge dietary response.

Dr. Thomas Dayspring: Believe it or not, since the half life of an LDL particle is three to five days, you can repeat it in a week to see what it’s doing. You get into trouble with third party payers saying, you can’t repeat this one test too often, but very quickly these metrics change. You don’t have to wait six months to see what you’re doing.

Dr. Kara Fitzgerald: And you know what, if you’ve got it, these are cheap tests. I mean, these are pretty inexpensive if you have to pay out of pocket.

Dr. Thomas Dayspring: Yes, they are.

Dr. Kara Fitzgerald: I would Direct Labs or something like that to get … And then follow until you have a dialed in. Listen, I want you to give me 30 seconds. I’m just going to jump over to what everyone’s thinking about right now, and that is, what about apoE4? We talked about it for a second. So within this context, you’re putting somebody on a keto, and they’re apoE4, so obviously you’re thinking about the lipids, you’re just going to do that. You’re going to be toggling them through the diet and then just do perhaps rapid fire ApoB measurement, right, to make sure they’re dialed in?

Dr. Thomas Dayspring: Well, yeah, you’re ultimately going to make the majority of your decisions on ApoB. And then you got to get into what is contributing to this high ApoB, and you’re going to get into a lot of factors there. Another topic for another day is your cholesterol homeostasis. Is your body over absorbing or over synthesizing cholesterol? I will tell you we have pretty good data from over 600,000 people that people within e4 allele tend to be hyper absorbers of cholesterol. So you can address that. Something else that would drive it would be over synthesizes of cholesterol, and one of the biggest stimulants that your cells start making too much cholesterol is you’re putting too much saturated fat into your diet, so that might be something that has to be assessed. And all of the other stuff that, Hey, apoE4 tells you whether you should eat fats or not comes from weak epidemiologic data where half of the trials show this, half of the trials don’t. So I personally don’t use …

The biggest thing I think you can do by apoE genotyping is pickup somebody with a one or two apoE4 alleles, then you know you have the potential for cognitive issues down the road, and you can interview them closely on their family history for that endpoint, and you can take issues. I believe cognitive impairment if discovered early enough is not an untreatable disease. I think there’s plenty of lifestyle, even supplemental things that you can do to ward that off. I think it’s crucial to know an Apoe4 on you, but for that reason, not that I’m going to use it to make dietary adjustments. And I know there are people who will disagree with me on that, but-

Dr. Kara Fitzgerald: You’re basically saying …

Dr. Thomas Dayspring: … they do not have high-level evidence.

Dr. Kara Fitzgerald: Yeah. So the jury is out, folks, as to what diet is appropriate for apoE4, you start somewhere and then you pay attention to the ApoB, etc., to make sure that apoE4 is dialed in.

Dr. Thomas Dayspring: That said whatever nutritional thing, and you know the world’s all over the map. I’ve got the best diet, you’ve got the best diet, do whatever you want to do nutritionally. And then a month later, two months at the outside, repeat some of these cardiovascular biomarkers. And are you succeeding or are you not? That’s easy.

Dr. Kara Fitzgerald: Yup. Yup. Perfect.

Dr. Thomas Dayspring: And if you’re not, change your therapy.

Dr. Kara Fitzgerald: Perfect. That’s easy. And you’ve given us some optimal ranges and we want them dialed in for these patients. All right. Listen, let’s talk a little bit about the LPA workup. So you’ve done this one time evaluation, LPA is high. Then what?

Dr. Thomas Dayspring: Well, right away we want to know this person is probably … you want a good family history. If you see ancestors have left the world earlier, had cardiovascular events, that even becomes a more significant risk factor, but not everybody knows their family history that well. In the real conundrum, it’s like everything else. Does everybody in the world who has high LDL cholesterol drop dead of a heart attack? No. Does everybody in the world who has high Lp(a) get cardiovascular events or aortic stenosis? No. Many do, but many do not. Well, the conundrum is here’s I see a patient with high Lp(a), I’m presuming their at cardiovascular risk, but how do I know? There’s a test. It’s common. Look, you’re going to assess all those other cardiovascular markers we’ve already talked about, and if they’re out of whack in a patient with Lp(a), I would treat them super aggressively cause they are modifiable, they are treatable, and by themselves if you improve them, they do reduce cardiovascular risk even in people with high Lp(a). But…

And this gets into a topic that’s probably best suited for another day. Those particles in the artery wall get oxidized and that’s what makes the macrophage ingest them causing form cells or plaque. We’d love to have tests of oxidized lipoproteins. The only one available now is something called oxidized LDL, which is basically looking at some oxidized aldehydes on ApoB that is on some of circulating LDL particles, and only those that are minimally oxidized, because there really are no fully oxidized particles circulating the plasma. It’s not a great blood test. I think it’s useful in that at least it tells you this person has a pro-oxidative state and you can address that, I think, with better nutrition than you can drugs, lifestyle, whole foods, etc., etc.

But Lp(a) is an LDL particle to which it’s attached an exogenous protein that shouldn’t be there, and it’s called apolipoprotein(a), Apo(a). Your liver makes it. It’s the only organ that makes it. So if you got the gene, say your liver makes Apo(a), it secretes it and that little Apo(a) jumps onto the first LDL particle it sees. Then it’s attached forever. And that Apo(a) has potentially thrombogenic properties, it’s a procoagulant, but its biggest detriment is probably a zillion years ago whenever primates evolved this, it’s function was to pick up oxidized lipids in your bloodstream, which are very toxic molecules and return them to the liver or some other tissue for catabolism. So if you have a CRO oxidative state, these oxidized, they’re mostly phospholipids, but other oxidized lipid moieties bind very closely to that Apo(a).

In general, if you have an Lp(a) particle that is also carrying oxidized phospholipids, that’s a way, way, way more dangerous Lp(a) particle. There is a blood test called O-X-P-L oxidized phospholipids-ApoB. They’re looking for oxidized phospholipids on ApoB particles. Virtually, all of those are Lp(a) particles. So right now at least proven in several published studies, if we could do oxidized phospholipids on ApoB, that would be a tremendous test for me to say, Oh my God, not only do you have too many Lp(a) particles, but they’re carrying oxidized lipids. That’s a really, really bad guy, we’ve got to get rid of it. That test hopefully will become available commercially this year. It’s been around for a long time. There’s a lot of research and publications on it, but it’s just … I know Boston Heart is trying to bring it to the real world and I hope they’re successful in doing that, because it’s a test you really need.

Without that, what I’d do with you if you have a high Lp(a) is I reduce your ApoB to physiological levels, or you’re not doing ApoB, I reduce your LDL cholesterol, non-HDL, cholesterol, triglycerides to physiological levels. I look for other inflammatory conditions, other things that might generate a pro oxidant state, insulin resistant being high on the list. Basically with high Lp(a), you’re trying to clean the body of every other thing that we know if we modulate them in the right direction, they reduce heart disease. And by the way, that’s why Lp(a) is not a goal of therapy at this time because we have nothing that has been proven to lower Lp(a) and reduce cardiovascular events, certainly because all of the therapies available nowadays just don’t lower Lp(a) enough.

The preliminary data, and we have a drug coming in, it’s going to stop your liver from making Apo(a) and we believe that’s going to be the cure of these people, but that’s years away. Until we have that, the studies at least with that drug show unless you reduce Lp(a) by 50 to 60 percent, you’re doing nothing beneficial to that patient. They still have enough Lp(a) particles left over to cause serious risks. So that’s the problem. We had nothing. So don’t be dwelling, staying up all night wondering how I can lower Lp(a). Lower ApoB. Get rid of the particles that are primarily driving your atherosclerosis, the VLDLs and LDLs. And that comes with LDL receptor mediated therapy, lifestyle or drugs, triglyceride lowering therapies, lifestyle or drugs, diabetes therapy that improve the lipids. And several diabetic therapies, at least in the pharmacologic world have now great cardiovascular event reduction data. So there’s many tools if you have to use them. That’s why early discovery is so crucial. That’s where the lifestyle is probably going to spare you a lifetime of taking drugs.

Dr. Kara Fitzgerald: Let me ask you this. This is very helpful because it’s true, anybody practicing medicine these days, we’re all looking at Lp(a), and the fact is, yeah, lowering it to levels associated with true risk reduction, that’s impossible.

Dr. Thomas Dayspring: It’s theory right now. That’s what it is, theory. There’s no proof of that.

Dr. Kara Fitzgerald: Well, let me ask you-

Dr. Thomas Dayspring: We all believe it’s true, but I would rather concentrate primarily on the things that get rid of the absolutely true risk factors. Then if you want to do something to lower Lp(a), be my guess. A popular therapy is Niacin. I never use Niacin. It’s just too toxic a molecule, but that’s again, another discussion.

Dr. Kara Fitzgerald: Right. I mean I do use Niacin and I just monitor liver function tests, but it’s still pretty challenging.

Dr. Thomas Dayspring: Yeah. But its commonest, biggest adversary is insulin resistance, osteogenic, erythmagenic, there’s just too much bad stuff seen in all the big Niacin trials. Look, if you’re going to use what they want, you got to watch for it.

Dr. Kara Fitzgerald: That’s a separate conversation. Yeah. Yeah. I will circle back on Niacin. All right. Well, listen, let me just ask you a couple of more questions on Lp(a) here in wrapping up. The fact that it’s associated with hypercoagulability, I mean am I looking at fibrinogen in my Lp(a) patients or am I using high-dose fish oil? I mean what are you thinking about with that?

Dr. Thomas Dayspring: Well, look, you can make the case for high-dose fish oil in virtually everybody with cardiovascular risk. Personally, I measure your red blood cell phospholipid Omega-3s, which is steady state of Omega-3s. And if it’s low, you need Omega-3s. If it’s not more, you probably don’t. But in general, that’s a very healthy cardiovascular supplement that I would recommend for most people to consider for their regimen, but actually a biomarker you can measure in the bloodstream. There’s just nothing that I can tell you nutritionally that, look, you’re going to prescribe nutrition based on all the other cardio-metabolic abnormalities you have found in your thorough workup or so. And then look, if Lp(a) doesn’t change, it goes up, it goes down, whoopsy do. You may be happy, we’re all happy to see something seemingly moving in the right direction. But all I’m asking you for, show me trials where some lowered Lp(a) and there are less heart attacks.

The only one even approaching that nowadays are the PCSK9 inhibitors and that’s because they blow away LDL so much, and because they’ve blown away LDL, they’re reducing some Lp(a) particles. Niacin has three trials where they looked at, they did Niacin to people with high Lp(a). And even though Niacin reduced it, there was no cardiovascular benefit. Who are you making happy when you prescribe Niacin, yourself, because you’re seeing a better Lp(a)? There wouldn’t be evidence supporting you. And I understand lots of people use it for that reason and that’s fine.

Dr. Kara Fitzgerald: Right. I hear you. Well, Mark Houston for one would be I think probably challenging you.

Dr. Thomas Dayspring: Yeah. He would be, but I would ask Mark, please forward me a study where Niacin improving Lp(a) matters. And Mark would have zero to send me. You do know prescription Niacin has been removed from the market in Europe, and it’s not recommended by any guideline here in the United States any longer.

Dr. Kara Fitzgerald: I want to talk about the coronary calcium score. If you see Lp(a), are you jumping on a calcium score immediately?

Dr. Thomas Dayspring: The most recent guidelines would tell you this, if you see somebody who has either an LDL cholesterol on an ApoB range that you don’t like, you think it’s predicting cardiovascular risk, of course you’re going to recommend a lifestyle change you want to. But sooner or later, depending on what the level of those metrics are, you’re going to say, we have to get into the world of pharmacotherapy if we’re ever going to get your ApoB to physiological levels. So you’re going to most likely go into Statin therapy as your first choice, you see, unless you’re very rich and you can go to a PCSK9 inhibitor. And as you know, not everybody wants to go on pharmacotherapy for lipid management. So how do you make that decision?

The guidelines say if you have somebody in the intermediate risk category with borderline LDL metrics, there’s two tests you can do that ascertain, yes, you have to go down the pharmacotherapy pathway. And the first is doing Lp(a) level. And if that’s high, you should go on a Statin. By the way, although Statins don’t lower Lp(a), they reduce LDL particle so much that there are cardiovascular benefits regardless of what the Statin does to Lp(a).

Dr. Kara Fitzgerald: What about the fact that you’re going to still see a whole lot of particles, LDL particles?

Dr. Thomas Dayspring: Well, remember of your total LDL particles, Lp(a) particles are maybe 10% of them. 90% of your LDL particle count, your ApoB is what, I don’t want to call normal, but they’re LDL particles not carrying Apo(a). So the Statins are great at clearing them. So they pull them out of your system, which drastically reduces your cardiovascular risk. They in general are not going to pull your Lp(a) particles, so they’re still there, but you certainly improve the cardiovascular risk of that patient by getting rid of the primary particles that are causing atherogenesis, the LDL and VLDL particles.

Remember, although Lp(a), it’s a minority LDL particle, nobody has a predominance of Lp(a) particles compared to LDL particles other than those who might be taking Statins and PCSK9 inhibitors. And so there’s still a little residual risk there. But until that Apo(a) synthesis inhibitor drug comes, you got nothing that you can address any Lp(a) issues with to at least … And that’s the hope. But listen, that’s three, four years away. They’re only doing this study in super high nightmare patients. It will tell us nothing about primary prevention with Lp(a). That is decades away before we have any proof from that, as sad as it sounds.

Dr. Kara Fitzgerald: Right. Right.

Dr. Thomas Dayspring: But you got to do what you got to do. This is why in the old days we could measure Lp(a) particle counts and LDL particle counts separately. That test is not available anymore. That could really tell you, wow, I’ve done a great job on lowering LDL particles, and as expected, I haven’t removed that many Lp(a) particles. But again, once you’ve gotten rid of the LDL particles and you’ve corrected insulin resistance, hypertension, other metabolic, then you’re stuck with your Lp(a).

Dr. Kara Fitzgerald: Right. Right. But you know what, then I think you’ve really considerably reduced risk when you dial all of those pieces in.

Dr. Thomas Dayspring: The important thing to know, I don’t want to downplay Lp(a), but even if you make all those other parameters normal, but Lp(a) is still an issue there, there is greater residual risks than in people who have no Lp(a). So it’s never not a bad particle. But I think in the future, we’re going to know the Lp(a)s you really have to worry about, those that are carrying oxidized phospholipids.  And again, I don’t know what you do for that either other than whole foods and reducing a pro-oxidant state or whatever supplements you might want to use for that.

Dr. Kara Fitzgerald: Yeah, that’s right. That’s right. You know what was interesting, I’m going to just ask you one last question then we’re already really at time.

Dr. Thomas Dayspring: Coronary calcium would follow, you said. What do you do? Everybody with a borderline LDL metric should have an Lp(a). The second test they recommend is a coronary calcium, because if that’s positive, you pretty much need serious pharmacotherapy on top of your lifestyle therapy to reduce your cardiovascular risk. If you have a coronary calcium is zero, you probably have 5 to 10 years before it’s going to come up with … People like Peter Attia would say, who cares? Atherosclerosis takes decades to develop. So why would you ever not want to treat a high ApoB? But they have to individualize that. If with zero coronary calcium, you might have some time to play. The other thing to recognize: coronary calcium is not a useful metric in young people because it does take decades to get a positive coronary calcium. So doing it in 20-year-olds is likely a waste of time.

Dr. Kara Fitzgerald: And are you going to be … What about actually turning it around?

Dr. Thomas Dayspring: In what way?

Dr. Kara Fitzgerald: I mean dropping up. I mean once you’ve got it, it’s there.

Dr. Thomas Dayspring: Here’s the problem, we’ve got any number of trials that show Statins increase coronary calcification, but they reduce cardiovascular events. Theory would be while the Statins and drug therapy are stabilizing your plaque, it’s not vulnerable plaque anymore, but stabilized plaque accumulates calcium. So as good as it is as a screening tool, I don’t believe it’s a tool that should be used for follow-up judging of your therapeutic efficacy of nutrition or drugs at this time. All you’re going to do is make a patient nervous. That doesn’t mean what you might think it means, because there are therapies that with increased coronary calcium that are cardioprotective.

Dr. Kara Fitzgerald: Okay. And that would just … as far as you’re concerned, that can be…

Dr. Thomas Dayspring: It’s like Lp(a). It’s a primary risk assessment tool. You don’t have to repeat it, either one of those. And one day we will repeat Lp(a) when we have a drug that says if you lower Lp(a) using this drug, there is cardiovascular risk reduction, and that’s a few years away.

Dr. Kara Fitzgerald: Okay. Well, this has been a Tour de force. I know everybody’s like fervently taking notes. We’ve got the transcript on the show notes, folks. I would love to talk to you on another call, some specific thoughts around women’s lipids. We won’t do that today, but I want to encourage the listeners to ping me with questions and your thoughts. I know for our functional medicine community, Dr. Dayspring has said some provocative things that might get a little bit of a fire going. Go ahead and post those comments. Dr. Dayspring can weigh in on it, and if you have additional comments and … Think about the women’s lipid podcast and questions you might have there as well. I just look forward to keeping this dialog going. It was extremely, extremely useful. Thank you. Thank you. Thank you for joining me today.

Dr. Thomas Dayspring: One more comment. I can be followed @drlipid on Twitter. I have over 12,000 followers. Every day I’m posting stuff that you’d probably find interesting whether you agree with it or not, but we all have a lot more to learn on these topics.

Dr. Kara Fitzgerald: Absolutely. And just your exquisite understanding of the biomarkers and how we want to look at them and how we want to think about them, it’s so, so invaluable to us. We will, Dr. Dayspring, print your Twitter, any information for folks to be able to follow you and access you, we’ll put all of that on our show notes. Thank you so much for joining me today and I look forward to continuing our conversation.

Dr. Thomas Dayspring: That was great, Kara. Thank you.

Dr. Kara Fitzgerald: And that wraps up another amazing conversation with a great mind in functional medicine. I am so glad that you could join me. None of this would be possible, through the years, without our generous, wonderful sponsors, including Integrative Therapeutics, Metagenics, and Biotics. These are companies that I trust, and I use with my patients, every single day. Visit them at IntegativePro.com, BioticsResearch.com, and Metagenics.com. Please tell them that I sent you and thank them for making New Frontiers in Functional Medicine possible.

And one more thing? Leave a review and a thumbs-up on iTunes or Soundcloud or wherever you’re hearing my voice. These kinds of comments will promote New Frontiers in Functional Medicine getting the word on functional medicine out there to greater community. And for that, I thank you.